The first aim of the studies described here is to define the role, if any, of lithocholic acid in liver injury or abnormal liver tests in patients participating in the National Cooperative Gallstone Study (NCGS). To do this, lithocholic acid levels in bile will be measured and related to documented liver injury (assessed by light and electron microscopy) as well as probable liver injury (inferred from elevated serum levels of alkaline phosphatase and/or bilirubin) and possible liver injury (inferred from elevated serum levels of transaminases). The second aim of the proposed studies is to determine whether the elevated serum aminotransferase levels indicate liver injury. This will be assessed by defining their relationship between elevations in the serum aminotransferase level and the fasting-state level of primary bile acids, as the liver is considered to be organ-specific and a moderately sensitive test of liver injury. Three specific hypotheses will be tested: (1) morphological liver damage whether documented by light or electron microscopy is associated with a significantly increased accumulation of lithocholic acid in the enterohepatic circulation, signalled by an increased proportion of lithocholate in biliary bile acids; (2) the self-limited elevations in serum aminotransferase level occurring during treatment with chenodeoxycholic acid in the NCGS do not reflect true liver injury, as these elevations are not associated with a parallel increase in the serum level of primary bile acids; (3) whenever liver damage occurs in NCGS patients, as documented either by a morphological abnormality noted in the liver biopsy or by an elevation in both serum aminotransferase and alkaline phosphatase levels, the level of immunoreactive serum bile acids is invariably increased.